RESUMO
We developed analytical expressions for the Wigner distribution function of partially coherent fields generated by the scattering of beams with a particular phase structure, namely perfect optical vortex beams. In addition, we provide the modal decomposition of the field correlations and evaluate the evolution of Shannon entropy associated with the partially coherent field.
RESUMO
BACKGROUND AND PURPOSE: Mitochondrial dysfunction contributes to the pathogenesis and maintenance of chemotherapy-induced peripheral neuropathy (CIPN), a significant limitation of cancer chemotherapy. Recently, the stimulation of mitophagy, a pivotal process for mitochondrial homeostasis, has emerged as a promising treatment strategy for neurodegenerative diseases, but its therapeutic effect on CIPN has not been explored. Here, we assessed the mitophagy-inducing activity of 3,5-dibromo-2-(2',4'-dibromophenoxy)-phenol (PDE701), a diphenyl ether derivative isolated from the marine sponge Dysidea sp., and investigated its therapeutic effect on a CIPN model. EXPERIMENTAL APPROACH: Mitophagy activity was determined by a previously established mitophagy assay using mitochondrial Keima (mt-Keima). Mitophagy induction was further verified by western blotting, immunofluorescence, and electron microscopy. Mitochondrial dysfunction was analysed by measuring mitochondrial superoxide levels in SH-SY5Y cells and Drosophila larvae. A thermal nociception assay was used to evaluate the therapeutic effect of PDE701 on the paclitaxel-induced thermal hyperalgesia phenotype in Drosophila larvae. KEY RESULTS: PDE701 specifically induced mitophagy but was not toxic to mitochondria. PDE701 ameliorated paclitaxel-induced mitochondrial dysfunction in both SH-SY5Y cells and Drosophila larvae. Importantly, PDE701 also significantly ameliorated paclitaxel-induced thermal hyperalgesia in Drosophila larvae. Knockdown of ATG5 or ATG7 abolished the effect of PDE701 on thermal hyperalgesia, suggesting that PDE701 exerts its therapeutic effect through mitophagy induction. CONCLUSION AND IMPLICATIONS: This study identified PDE701 as a novel mitophagy inducer and a potential therapeutic compound for CIPN. Our results suggest that mitophagy stimulation is a promising strategy for the treatment of CIPN and that marine organisms are a potential source of mitophagy-inducing compounds.
RESUMO
Mitophagy induction upon mitochondrial stress is critical for maintaining mitochondrial homeostasis and cellular function. Here, we found that Mst1/2 (Stk3/4), key regulators of the Hippo pathway, are required for the induction of mitophagy under various mitochondrial stress conditions. Knockdown of Mst1/2 or pharmacological inhibition by XMU-MP-1 treatment led to impaired mitophagy induction upon CCCP and DFP treatment. Mechanistically, Mst1/2 induces mitophagy independently of the PINK1-Parkin pathway and the canonical Hippo pathway. Moreover, our results suggest the essential involvement of BNIP3 in Mst1/2-mediated mitophagy induction upon mitochondrial stress. Notably, Mst1/2 knockdown diminishes mitophagy induction, exacerbates mitochondrial dysfunction, and reduces cellular survival upon neurotoxic stress in both SH-SY5Y cells and Drosophila models. Conversely, Mst1 and Mst2 expression enhances mitophagy induction and cell survival. In addition, AAV-mediated Mst1 expression reduced the loss of TH-positive neurons, ameliorated behavioral deficits, and improved mitochondrial function in an MPTP-induced Parkinson's disease mouse model. Our findings reveal the Mst1/2-BNIP3 regulatory axis as a novel mediator of mitophagy induction under conditions of mitochondrial stress and suggest that Mst1/2 play a pivotal role in maintaining mitochondrial function and neuronal viability in response to neurotoxic treatment.
Assuntos
Mitofagia , Neuroblastoma , Proteínas Serina-Treonina Quinases , Serina-Treonina Quinase 3 , Animais , Humanos , Camundongos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Mitofagia/genética , Mitofagia/fisiologia , Neurônios/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Serina-Treonina Quinase 3/genética , Serina-Treonina Quinase 3/metabolismo , Drosophila/genéticaRESUMO
Connectomics research has made it more feasible to explore how neural circuits can generate multiple outputs. Female sexual drive provides a good model for understanding reversible, long-term functional changes in motivational circuits. After emerging, female flies avoid male courtship, but they become sexually receptive over 2 d. Mating causes females to reject further mating for several days. Here, we report that pC1 neurons, which process male courtship and regulate copulation behavior, exhibit increased CREB (cAMP response element binding protein) activity during sexual maturation and decreased CREB activity after mating. This increased CREB activity requires the neuropeptide Dh44 (Diuretic hormone 44) and its receptors. A subset of the pC1 neurons secretes Dh44, which stimulates CREB activity and increases expression of the TRP channel Pyrexia (Pyx) in more pC1 neurons. This, in turn, increases pC1 excitability and sexual drive. Mating suppresses pyx expression and pC1 excitability. Dh44 is orthologous to the conserved corticotrophin-releasing hormone family, suggesting similar roles in other species.
Assuntos
Proteínas de Drosophila , Neuropeptídeos , Animais , Masculino , Feminino , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/metabolismo , Neuropeptídeos/metabolismo , Copulação/fisiologia , Corte , Hormônios , Comportamento Sexual Animal/fisiologiaRESUMO
Palmatine, a natural alkaloid found in various plants, has been reported to have diverse pharmacological and biological effects, including anti-inflammatory, antioxidant, and cardiovascular effects. However, the role of palmatine in mitophagy, a fundamental process crucial for maintaining mitochondrial function, remains elusive. In this study, we found that palmatine efficiently induces mitophagy in various human cell lines. Palmatine specifically induces mitophagy and subsequently stimulates mitochondrial biogenesis. Palmatine did not interfere with mitochondrial function, similar to CCCP, suggesting that palmatine is not toxic to mitochondria. Importantly, palmatine treatment alleviated mitochondrial dysfunction in PINK1-knockout MEFs. Moreover, the administration of palmatine resulted in significant improvements in cognitive function and restored mitochondrial function in an Alzheimer's disease mouse model. This study identifies palmatine as a novel inducer of selective mitophagy. Our results suggest that palmatine-mediated mitophagy induction could be a potential strategy for Alzheimer's disease treatment and that natural alkaloids are potential sources of mitophagy inducers.
Assuntos
Alcaloides , Doença de Alzheimer , Camundongos , Animais , Humanos , Mitofagia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Mitocôndrias/metabolismo , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Alcaloides/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Mitophagy stimulation has been shown to have a therapeutic effect on various neurodegenerative diseases. However, nontoxic mitophagy inducers are still very limited. In this study, we found that the natural alkaloid berberine exhibited mitophagy stimulation activity in various human cells. Berberine did not interfere with mitochondrial function, unlike the well-known mitophagy inducer carbonyl cyanide m-chlorophenyl hydrazone (CCCP), and subsequently induced mitochondrial biogenesis. Berberine treatment induced the activation of adenosine monophosphate-activated protein kinase (AMPK), and the AMPK inhibitor compound C abolished berberine-induced mitophagy, suggesting that AMPK activation is essential for berberine-induced mitophagy. Notably, berberine treatment reversed mitochondrial dysfunction in PINK1 knockout mouse embryonic fibroblasts. Our results suggest that berberine is a mitophagy-specific inducer and can be used as a therapeutic treatment for neurodegenerative diseases, including Parkinson's disease, and that natural alkaloids are potential sources of mitophagy inducers.
Assuntos
Berberina , Doenças Mitocondriais , Doença de Parkinson , Animais , Humanos , Camundongos , Camundongos Knockout , Berberina/farmacologia , Proteínas Quinases Ativadas por AMP , Mitofagia , Fibroblastos , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologiaRESUMO
Paclitaxel is a widely used anticancer drug that induces dose-limiting peripheral neuropathy. Mitochondrial dysfunction has been implicated in paclitaxel-induced neuronal damage and in the onset of peripheral neuropathy. We have previously shown that the expression of PINK1, a key mediator of mitochondrial quality control, ameliorated the paclitaxel-induced thermal hyperalgesia phenotype and restored mitochondrial homeostasis in Drosophila larvae. In this study, we show that the small-molecule PINK1 activator niclosamide exhibits therapeutic potential for paclitaxel-induced peripheral neuropathy. Specifically, niclosamide cotreatment significantly ameliorated the paclitaxel-induced thermal hyperalgesia phenotype in Drosophila larvae in a PINK1-dependent manner. Paclitaxel-induced alteration of the dendrite structure of class IV dendritic arborization (C4da) neurons was not reduced upon niclosamide treatment. In contrast, paclitaxel treatment-induced increases in both mitochondrial ROS and aberrant mitophagy levels in C4da neurons were significantly suppressed by niclosamide. In addition, niclosamide suppressed paclitaxel-induced mitochondrial dysfunction in human SH-SY5Y cells in a PINK1-dependent manner. These results suggest that niclosamide alleviates thermal hyperalgesia by attenuating paclitaxel-induced mitochondrial dysfunction. Taken together, our results suggest that niclosamide is a potential candidate for the treatment of paclitaxel-induced peripheral neuropathy with low toxicity in neurons and that targeting mitochondrial dysfunction is a promising strategy for the treatment of chemotherapy-induced peripheral neuropathy.
RESUMO
PURPOSE: To evaluate the effectiveness of preoperative lacrimal endoscopic evaluation (LEE) of lacrimal duct system (LDS). DESIGN: Retrospective comparative case series METHODS: From March 2016 to February 2020, the charts of patients chosen to undergo endoscopic dacryocystorhinostomy (EDCR) or silicone tube intubation (STI) were reviewed retrospectively. Group 1 included patients that underwent EDCR, and group 2 included patients that underwent STI. Preoperative LEE was performed for all patients. In group 1, we compared the functional success rate for patients who had been converted to STI with the patients who had undergone EDCR. In group 2, we compared the functional success rate of STI with those who had had STI without LEE. RESULTS: In group 1, 19 (54.3%) eyes were converted to STI following LEE, and the functional success rate was 84.2%, which is not significantly different from that of the EDCR group following LEE (p = 0.608). The functional success rate of EDCR without LEE was not different from that of STI following LEE (p = 1.000). In group 2, five eyes (26.3%) were converted to EDCR following LEE. The group undergoing STI following LEE showed a significantly higher functional success rate (95.7%) than the group without LEE (66.6%, p = 0.023). CONCLUSION: Preoperative LEE enables direct visualization of the LDS and helps to obtain more accurate diagnosis. This allows for the best surgical option based on LEE findings, which can contribute to better results. Therefore, LEE would be expected to change the paradigm of the classical management of LDS.
Assuntos
Dacriocistorinostomia , Aparelho Lacrimal , Obstrução dos Ductos Lacrimais , Ducto Nasolacrimal , Endoscopia , Pálpebras , Humanos , Aparelho Lacrimal/diagnóstico por imagem , Aparelho Lacrimal/cirurgia , Obstrução dos Ductos Lacrimais/diagnóstico , Obstrução dos Ductos Lacrimais/terapia , Ducto Nasolacrimal/diagnóstico por imagem , Ducto Nasolacrimal/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Although low-cost, high-surface-area crystalline aluminosilicate zeolites have been recognized as promising adsorbents for the capture of volatile organic compounds (VOCs), their hydrophilic nature leads to a significant loss of performance owing to the ubiquitous presence of water vapor in the VOC stream. Herein, the aluminosilicate zeolites (i.e., mordenite and nanocrystalline ß) are functionalized via a solvothermal post-treatment with methyl iodide as the grafting agent. The methyl groups are primarily attached to the zeolite internal surface via covalent bonding between internal bridging O and -CH3, as evidenced by multiple analysis data. The static isotherms and diffusional studies clearly reveal a remarkable decrease in both the rate of water adsorption and the water affinity due to the attachment of methyl groups to the micropore walls, thus enhancing the water tolerance compared to that of pristine zeolites. In addition, CH3I-functionalized zeolites are investigated as adsorbents for the removal of benzene under dry and humid conditions, and their performance is compared to that of CH3Si(-OCH3)3-functionalized zeolites, wherein the methyl groups have been grafted onto the external surface. The results demonstrate that, although the benzene adsorption capacity under dry conditions is decreased upon internal surface functionalization, the loss of VOC adsorption capacity in the presence of H2O vapor is effectively prevented. By contrast, external surface functionalization is ineffective for preventing the negative effects of moisture upon the benzene adsorption capacity. As a result, CH3I-functionalized zeolites exhibit superior dynamic adsorption performance for benzene at 318 K under humid conditions (relative humidity: 80%), with a saturated adsorption capacity of 64.9 mg g-1. This work provides an easy strategy for tailoring the adsorption properties of aluminosilicate zeolites for adsorption/separation and other advanced applications.
RESUMO
To realize efficient operation of a silo, level management of internal storage is crucial. In this study, to address the existing measurement limitations, a silo hotspot detector, which is typically utilized for internal silo temperature monitoring, was employed. The internal temperature data measured using the hotspot detectors were used to train an artificial neural network (ANN) algorithm to predict the level of the internal storage of the silo. The prediction accuracy was evaluated by comparing the predicted data with ground truth data. We combined the ANN model with the genetic algorithm (GA) to improve the prediction accuracy and establish efficient sensor installation positions and number to proceed with optimization. Simulation results demonstrated that the best predictive performance (up to 97% accuracy) was achieved when the ANN structure was 9-19-19-1. Furthermore, the numbers of efficient sensors and sensors positions determined using the proposed ANN-GA technique were reduced from seven to five or four, thereby ensuring economic feasibility.
Assuntos
Algoritmos , Redes Neurais de Computação , Simulação por ComputadorAssuntos
Glaucoma , Hipertensão Ocular , Humanos , Pressão Intraocular , Diálise Renal/efeitos adversosRESUMO
In Asia, Vigna angularis (azuki bean) has been used as a traditional medicine to treat various diseases because of its biological properties. Osteoarthritis (OA) and osteoporosis (OP) are common regenerative bone diseases that are characterized by deterioration of joint and bone structure. In this study, we evaluated the effects of Vigna angularis extract (VAE) on monosodium iodoacetate (MIA)-induced OA and ovariectomy (OVX)-induced OP models. In the MIA-induced OA results, severe OA was alleviated by the administration of VAE. Extensive local damage in the cartilage and hemorrhagic and edematous of surrounding tissues were decreased by VAE treatment. Articular cartilage was almost intact except for a focal mild abrasion, and the surface was glistening, similar to that of the normal joint. In the OVX-induced OP results, bone mineral content (BMC) and bone mineral density (BMD) were recovered by VAE treatment, and it improved the microstructures of bone. These results show that VAE could inhibit OA and OP symptoms.
RESUMO
Eudebeiolide B is a eudesmane-type sesquiterpenoid compound isolated from Salvia plebeia R. Br., and little is known about its biological activity. In this study, we investigated the effects of eudebeiolide B on osteoblast differentiation, receptor activator nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro and ovariectomy-induced bone loss in vivo. Eudebeiolide B induced the expression of alkaline phosphatase (ALP) and calcium accumulation during MC3T3-E1 osteoblast differentiation. In mouse bone marrow macrophages (BMMs), eudebeiolide B suppressed RANKL-induced osteoclast differentiation of BMMs and bone resorption. Eudebeiolide B downregulated the expression of nuclear factor of activated T-cells 1 (NFATc1) and c-fos, transcription factors induced by RANKL. Moreover, eudebeiolide B attenuated the RANKL-induced expression of osteoclastogenesis-related genes, including cathepsin K (Ctsk), matrix metalloproteinase 9 (MMP9) and dendrocyte expressed seven transmembrane protein (DC-STAMP). Regarding the molecular mechanism, eudebeiolide B inhibited the phosphorylation of Akt and NF-κB p65. In addition, it downregulated the expression of cAMP response element-binding protein (CREB), Bruton's tyrosine kinase (Btk) and phospholipase Cγ2 (PLCγ2) in RANKL-induced calcium signaling. In an ovariectomized (OVX) mouse model, intragastric injection of eudebeiolide B prevented OVX-induced bone loss, as shown by bone mineral density and contents, microarchitecture parameters and serum levels of bone turnover markers. Eudebeiolide B not only promoted osteoblast differentiation but inhibited RANKL-induced osteoclastogenesis through calcium signaling and prevented OVX-induced bone loss. Therefore, eudebeiolide B may be a new therapeutic agent for osteoclast-related diseases, including osteoporosis, rheumatoid arthritis and periodontitis.
RESUMO
Phenolics from plant materials have garnered attention in nanomedicine research, due to their various medicinal properties. Caffeic acid, a phenolic compound that is abundant in coffee beans, has been proven to have anticancer effects, due to its reactive oxygen species (ROS)-inducing properties. Here, a supramolecular nanomedicine was designed using caffeic acid molecule and the synthetic anticancer drug bortezomib, via catechol-boronic acid conjugation and Fe(III) ion crosslinking. Bortezomib is a proteasome-inhibiting drug and its boronic acid functional group can bind to caffeic acid's catechol moiety. By having a nanoparticle formulation that can deliver bortezomib via intracellular endocytosis, the catechol-boronic acid conjugation can be dissociated, which liberates the boronic acid functional group to bind to the 26S proteasome of the cell. The ROS-inducing property of caffeic acid also complements the bortezomib payload, as the latter suppresses the survival mechanism of the cell through NF-κB inhibition.
RESUMO
Many studies have reported the biological activities of retrofractamide C (RAC). However, few studies have investigated the anti-inflammatory effect of RAC. In the present study, we investigated the anti-inflammatory effect of RAC using lipopolysaccharide (LPS)-induced J774A.1 cells and a xylene-induced mouse ear edema model. Treatment with RAC decreased LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) secretion and inducible NO synthase (iNOS) and cyclooxygenase 2 (COX2) protein expression. It also downregulated the LPS-induced production of interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) but not tumor necrosis factor α (TNF-α). In the LPS-induced signaling pathway, RAC inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) but not c-Jun N-terminal kinase (JNK) or p38. In a xylene-induced mouse ear edema model, RAC treatment alleviated edema formation and inflammatory cell infiltration. In conclusion, the present study indicates that RAC has the potential to have anti-inflammatory effects and could be a prospective functional food.
Assuntos
Amidas/farmacologia , Orelha/patologia , Edema/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Piper/química , Amidas/química , Animais , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Camundongos Endogâmicos ICR , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Xilenos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
A novel hypochlorous-acid-selective signaling probe based on the carbonodithioate derivative of resorufin (RT-1) was developed. Probe RT-1 showed prominent colorimetric and turn-on type fluorescence signaling behavior exclusively toward hypochlorous acid, induced by oxidative hydrolysis, to regenerate resorufin dye. Hypochlorous acid signaling was not affected by the presence of common metal ions and anions as background, except for the redox active bromide and iodide anions. The detection limit of RT-1 for hypochlorous acid was found to be 2.18 × 10-9 M (0.11 ppb), and the signaling was completed within 3 min. It was also confirmed that hypochlorous acid signaling by the carbonodithioate-based probe RT-1 was superior to that of the closely related carbonothioate derivative RT-2. This was rationalized by density functional theory calculations, which demonstrated that the C[double bond, length as m-dash]S sulfur atom of the former is more negatively charged than that of the latter. Finally, as a biological application of the probe, visualization of hypochlorous acid in RAW 264.7 murine macrophages and HeLa cells was successfully conducted to detect the cellular response to hypochlorous acid.
Assuntos
Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Oxazinas/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Colorimetria/métodos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Limite de Detecção , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Oxazinas/síntese química , Oxazinas/toxicidade , Células RAW 264.7RESUMO
Many studies have identified and described various medicinal effects of cirsiliol. Here, we investigated the signaling pathway involved in the anti-inflammatory effects of cirsiliol on IL-6-induced activity. Cirsiliol showed no cytotoxicity and inhibited pSTAT3-induced luciferase activity. At the molecular level, cirsiliol suppressed the expression of IL-6-induced inflammatory marker genes such as CRP, IL-1ß, ICAM-1 and SOCS3, IL-6-induced activation of Jak2, gp130, STAT3 and ERK and nuclear translocation of STAT3, as measured by PCR, immunofluorescence staining and western blot analysis. However, the interaction between IL-6 and its receptor was not affected by cirsiliol treatment. These results indicate that cirsiliol attenuates IL-6-induced cellular signaling by regulating Jak2 phosphorylation. Therefore, cirsiliol could be a therapeutic agent for IL-6-related inflammatory diseases.
Assuntos
Anti-Inflamatórios/uso terapêutico , Flavonas/uso terapêutico , Interleucina-6/metabolismo , Fator de Transcrição STAT3/metabolismo , Anti-Inflamatórios/farmacologia , Flavonas/farmacologia , Humanos , Técnicas In VitroRESUMO
BACKGROUND: /Objective: The conventional models currently used to evaluate various anti-tumor therapeutic agents are not sufficient for representing human pancreatic ductal adenocarcinoma (PDA), which has a unique tumor microenvironment. We aimed to produce an organotypic slice culture model from human PDA that resembles the in vivo situation and to evaluate the responses of PDA slices to established cytotoxic drugs. METHODS: PDA tissues were obtained from 10 patients who underwent pancreatic resection. The tissues were sliced by a vibratome, and the tumor slices were then cultured. The viability of tumor slices during slice culture was evaluated using H&E and immunohistochemical staining, and stromal cells were demonstrated. The effects of cytotoxic drugs on PDA cell lines and slices were analyzed. RESULTS: Tumor slices maintained their surface areas and tissue viability for at least five days during culture. Preserved proliferation and apoptosis in tumor slices were observed by the expression of Ki-67 and cleaved caspase-3. Stromal cells including macrophages (CD68+ and CD163+), T cells (CD3+, CD8+, and FOXP3+), and myeloid cells (CD11b+) were present throughout the culture period. Staurosporine, gemcitabine, and cisplatin treatment of PDA cell lines and tumor slices exerted proportional cytotoxic effects in terms of MTT viability, tumor cell number, and Ki-67 and cleaved caspase-3 expression. CONCLUSIONS: Organotypic human PDA slice cultures preserved their viability and tumor microenvironment for at least five days during slice culture. PDA slice culture appears to be a feasible preclinical test model to assess the response to anti-tumor agents.
Assuntos
Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Microambiente Tumoral , Idoso , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Chemotherapy frequently causes anorexia in cancer patients, which has been associated with poor disease prognosis. Several therapeutic strategies for the treatment of chemotherapyinduced anorexia are available; however, their adverse effects limit their clinical use. Herbal medicines have a long history of use for the treatment of various diseases, including cancer, and recent research has demonstrated their safety and efficacy. In the present study, combinations of herbal medicines were designed based on traditional Korean medicine, and their effects were investigated on chemotherapyinduced anorexia. Herbal mixtures were extracted, composed of Atractylodes japonica, Angelica gigas, Astragalus membranaceus, Lonicera japonica Thunb., Taraxacum platycarpum H. Dahlstedt and Prunella vulgaris var. asiatica (Nakai) Hara. The mixtures were termed LCBPAnocure160013 (LA16001, LA16002, LA16003). A cisplatininduced anorexic mouse model was used to evaluate the putative effects of the extracts on chemotherapyinduced anorexia. Treatment with LA16001 was revealed to prevent body weight loss, and all three extracts were demonstrated to improve food intake. When the molecular mechanisms underlying the orexigenic effects of LA16001 were investigated, altered expression levels of ghrelin, leptin and interleukin6 were revealed. Furthermore, LA16001 was reported to induce phosphorylation of Janus kinase 1 and signal transducer and activator of transcription 3. In addition, LA16001 administration increased the number of white blood cells and neutrophils. These results suggested that the herbal formula LA16001 may be able to prevent chemotherapyinduced anorexia and may have potential as a novel therapeutic strategy for the adjuvant treatment of patients with cancer.
Assuntos
Anorexia/etiologia , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Extratos Vegetais/farmacologia , Animais , Anorexia/tratamento farmacológico , Anorexia/metabolismo , Apetite/efeitos dos fármacos , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Medicina Herbária , Hormônios/metabolismo , Humanos , Janus Quinase 1/metabolismo , Masculino , Camundongos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND/AIMS: As the prevalence of diabetes mellitus and its complications increase rapidly, diabetic foot ulcers (DFUs), which are a major diabetic complication, are expected to increase. For prevention and effective treatment, it is important to understand the clinical course of DFUs. The aim of this study was to investigate the natural course and predictors of amputation in patients with DFUs who required hospitalization. METHODS: A total of 209 patients with type 2 diabetes, aged 30 to 85 years, who visited emergency department or needed hospitalization due to DFUs were consecutively enrolled from May 2012 to January 2016, by retrospective medical record review. The main outcome was lower extremity amputation (LEA). RESULTS: Among 192 patients who completed follow-up, 113 patients (58.9%) required LEAs. Compared to patients without amputation, baseline levels of white blood cell counts and C-reactive protein were higher in patients with amputation. In addition, bone and joint involvement was more frequently observed in patients with amputation. Multivariable regression analysis revealed that combined infection (odds ratio [OR], 11.39; 95% confidence interval [CI], 2.55 to 50.93; p = 0.001) and bone or joint involvement (OR, 3.74; 95% CI, 1.10 to 12.70; p = 0.035) were significantly associated with an increased risk of LEA. CONCLUSION: The depth of the wound and combined infection of DFU, rather than the extent of the wound, were significant prognostic factors of LEAs in patients with type 2 diabetes.